As synthetic processes of D-biotin, for example, the process using a sugar as a starting material [Tetrahedron Letters, 2765 (1975)] and a process using L-cysteine as a starting material [J. Am. Chem. Soc., 97, 5936 (1975)] have been known. In these processes, optically active compounds are used as the starting materials and optically active D-biotin is obtained by stereoselective reactions.
Further, as other processes for producing D-biotin, there are, for example, a process wherein D-biotin is prepared by using an optically active lactone obtained by selective reduction of only a carboxyl group of a half ester according to the following reaction scheme (JP-A 59-84888): ##STR3## and a process wherein D-biotin is prepared by using an optically active lactone obtained from an optically active amidecarboxylic acid by esterification, reduction and hydrolysis according to the following reaction scheme (JP-B 60-3387): ##STR4##
JP-A 57-198098 discloses the production of an optically active monoester mono carboxylic acid by hydrolyzing the corresponding diester asymmetrically using an esterase. The optically active monoester-mono-carboxylic acid can be converted into cis-1,3-dibenzylhexahydro 1H-furo(3,4d)-imidazole 2,4-dione which is used as an intermediate for D-biotin synthesis by lactonization with lithium borohydride.
Furthermore, Tetrahedron, 46, 7667 (1990) discloses a process for producing D-biotin according to the following reaction scheme: ##STR5## and a process for producing the above halide by reduction of a compound of the formula: ##STR6## with triethylsilane, boron trifluoride followed by halogenation.
However, these processes are not suitable for the industrial production of D-biotin because each of them includes many reaction steps, reaction operations are complicated, and further the total yield is low.
Under these circumstances, the present inventors have studied D-biotin synthesis and investigated industrially advantageous processes for the production of optical active intermediates, intensively. As a result, it has been found that kinetic optical resolution using an enzyme as a catalyst is very advantageous to the production of intermediates for D-biotin synthesis. The present inventors have further continued the investigation based on this finding and have found a novel intermediate for D-biotin synthesis which is very useful for the kinetic optical resolution. When the novel intermediate is subjected to the kinetic optical resolution and then to a series of reactions, D-biotin having high optical purity can be obtained in high yield. Further, when this novel intermediate for D-biotin synthesis is used and an enzyme is suitably selected, the kinetic optical resolution can be efficiently employed in both hydrolysis of the novel intermediate and the production of the novel intermediate by acylation.
In this respect, recently, acylation catalyzed by an enzyme such as lipase or the like in an organic solvent have been reported one after another [J. Am. Chem. Soc., 113, 3166 (1991); Tetrahedron Letters, 33, 3231 (1992); etc.]. However, there are not so many enzymes which can exhibit their activities in an organic solvent and their use is restricted. Nevertheless, the above acylation can be efficiently carried out.
By the way, a biggest defect of optical resolution is that only one half of a starting material is utilized. The present inventors have also studied to overcome this problem. As a result, it has been found that the enantiomeric intermediate synthesis removed by the optical resolution can be used again as a starting material for the production of the novel intermediate for D-biotin synthesis by subjecting the enantiomeric intermediate to deacyloxylation. As a similar method, the above reduction of the hydroxy group with triethylsilane and boron trifluoride [Tetrahedron, 46, 7667 (1990)] has been reported. However, these reagents are expensive and can not be readily available. Further, they have high reactivity, which makes their handling very difficult. Furthermore, the reaction should be carried our under anhydrous conditions at a lower temperature. Therefore, it is not suitable for the industrial production.
Further, it has been found a certain known intermediate for D-biotin synthesis can be efficiently converted into another known intermediate useful for D-biotin synthesis by specific oxidation. As similar oxidation, Swern oxidation using dimethylsulfoxide (DMSO) and trifluoroacetic anhydride has been known [Tetrahedron, 46, 7667 (1990)]. However, since trifluoroacetic anhydride is expensive and the reaction should be carried out at a low temperature such as -60.degree. C., it is not suitable for the industrial production. On the other hand, as a cheaper oxidizing agent with easy handling properties, a combination of DMSO and an activating agent has been known. Oxidation using such an oxidizing agent is known as Albright-Goldman oxidation and is advantageous because it can be carried out at room temperature. However, this oxidation is effective for only alcohols having large steric hindrance and, in the case of other compounds, the formation of by-products such as methylthiomethyl ether isomers and the like have been reported [J. Am. Chem. Soc., 87, 4214 (1965); Jikken Kagaku Koza, 4th ed., Vol. 23, p 318]. When this oxidation was applied to 4-hydroxyl group of the compound (II') as described hereinafter, acetylation predominantly proceeded and only a little objective compound was obtained. Nevertheless, when this oxidation is applied to the production of the above intermediate for D-biotin production under conditions different from ordinary employed conditions, surprisingly, the intermediate can be obtained with minimizing the formation of by-products and the desired oxidation product can be obtained in high yield.